PPOM 1 Week 20 LEC 183-192

(183) Trigger Point

hyperirritable spot in a taut band of a skeletal muscle that is painful on compression, stretch, overload or contraction of the tissue which usually responds with a referred pain that is perceived distant from the spot

(183) Jump Sign

patient pain response (wincing, withdrawal response)

(183) Local Twitch Response

transient contraction of the taut band of muscle where the trigger point is located

(183) Diagnosis of Trigger Points

palpated as small nodular or spindle-shaped thickenings within a taut band of tissue; Palpate by applying pressure perpendicular to the long axis of the muscle

(183) Myofascial Pain Syndrome (MPS)

The sensory, motor, and autonomic symptoms caused by myofascial trigger points, in a specific muscle or muscle group

(183) Active Trigger Point

Type of Trigger Point, Refers or produces a patient’s familiar pain (or patient’s other referred symptoms); Spontaneous local or referred pain

(183) Latent Trigger Point

Type of Trigger Point, Local or referred unfamiliar pain; Painful only when palpated or needled

(183) Counterstrain Points are:

similar to trigger points, but different in that they do not cause referred pain

(183) Fibromyalgia Tender Points are:

similar to trigger points, but different in that they often include a total body increase in pain sensitivity

(184) HIV life cycle

(1) Entry (binding and fusion to host cell), (2) reverse transcription, (3) integration of HIV cDNA into host genome, (4) replication (transcription and translation), (5) assembly and budding (6) maturation

(184) Antiretroviral Therapy (ART) resistance

HIV reverse transcriptase is error prone and lacks a proofreading function. Mutation is frequent. Drug therapy ultimately provides the necessary selective pressure to promote growth of drug-resistant viruses that arise naturally.

(184) Resistance testing

Important to help guide treatment decisions in both treatment-naïve and treatment-experienced patients

(184) Goal of Antiretroviral Therapy (ART)

To restore immunocompetence – increase the CD4 cell count and reduce viral load to undetectable (suppression of HIV RNA replication), reduce HIV-associated morbidity and prolong the duration and quality of survival, and prevent HIV transmission

(184) (185) Antiretroviral Therapy (ART) Drug classes

nucleoside reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), nonnucleoside/tide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), entry inhibitors, and capsid inhibitor

(184) (185) Pharmacokinetic enhancers (“Boosters”)

Potent CYP3A4 and P-gp inhibitors, which increases systemic levels of the partner drug allowing for less frequent dosing and less variation in drug levels, resulting in enhanced efficacy and reduced resistance

(184) (185) Examples of Pharmacokinetic enhancers (“Boosters”)

Ritonavir, Cobicistat

(185) Examples of First-generation nucleoside reverse transcriptase inhibitors (NRTIs)

Zidovudine

(184) Examples of Second-generation nucleoside reverse transcriptase inhibitors (NRTIs)

tenofovir (TDF and TAF), emtricitabine, lamivudine, abacavir

(184) Mechanism of Action of nucleoside reverse transcriptase inhibitors (NRTIs)

nucleoside analogs, except tenofovir which is a nucleotide analog

(184) _____ can cause proximal renal tubulopathy and bone loss.

Tenofovir DF (TDF)

(184) _____ is indicated as HIV/HBV treatment in Children ≥2 years old.

Tenofovir DF (TDF)

(184) _____ is administered in lower doses and has less long-term kidney and bone toxicity.

Tenofovir AF (TAF)

(184) _____ is indicated as HIV/HBV treatment in Children, adolescents ≥12 years old.

Tenofovir AF (TAF)

(184) _____ can cause a life-threatening hypersensitivity reaction. Patients should be screened for HLA-B*5701 allele.

Abacavir

(184) Examples of integrase strand transfer inhibitors (INSTIs)

Bictegravir, Dolutegravir, Elvitegravir, Raltegravir, Cabotegravir

(184) Adverse Effects of Integrase Strand Transfer Inhibitors (INSTIs)

Headache and GI effects

(185) Adverse Effects of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

associated with varying degrees of GI intolerance and skin rash. Metabolized by, and are inhibitors and inducers of, various CYPs; high potential for drug-drug interactions

(185) Adverse Effects of protease inhibitors (PIs)

Insulin resistance, hyperglycemia, diabetes, hyperlipidemia, lipodystrophy, hepatotoxicity, bleeding in patients with hemophilia, and PR interval prolongation. high potential for drug-drug interactions

(184) _____ can cause QT interval prolongation and is associated with neurological and psychiatric side effects.

Efavirenz, Rilpivirine

(185) _____ has been associated with severe hepatoxicity and related rash or fever. Liver function monitoring is recommended.

Maraviroc

(185) _____ is a peptide given by subcutaneous injection twice daily and often causes local cutaneous reactions.

Enfuvirtide

(185) _____ is an oral prodrug for temsavir.

Fostemsavir

(185) Adverse Effects of Fostemsavir

nausea, QT interval prolongation and elevated liver enzymes in patients with hepatitis B or hepatitis C viral infections; Strong CYP3A4 inducers should be avoided

(185) Adverse Effects of Ibalizumab

diarrhea, dizziness, nausea, rash

(185) _____ is given by intravenous infusion every 2 weeks.

Ibalizumab

(184) Mechanism of Action of Lenacapavir

Capsid inhibitor; directly binds the interface between capsid protein (p24) subunits in hexamers, changing its conformation, which stabilizes it, prevents viral uncoating, and disrupts the viral lifecycle at several steps

(184) M184V/I single amino acid substitution confers high-level resistance to these NRTIs:

Lamivudine, Emtricitabine

(184) First line Integrase strand transfer inhibitors (INSTIs):

Bictegravir, Dolutegravir

(184) M184V/I single amino acid substitution confers low-level resistance to these NRTIs:

Abacavir

(184) _____ is metabolized by alcohol dehydrogenase and glucuronyl transferase.

Abacavir

(184) M184V/I single amino acid substitution restores susceptibility to these NRTIs:

Tenofovir

(184) _____ treatment should be suspended in the setting of rapidly rising aminotransferase levels, progressive hepatomegaly, or metabolic acidosis of unknown cause

Nucleoside Reverse Transcriptase Inhibitor (NRTI)

(184) _____ treatment is well tolerated, highly effective, and has a high barrier to resistance.

Integrase Strand Transfer Inhibitor (INSTI)

(184) These drugs are Cytidine analogs and should not be used together:

Lamivudine, Emtricitabine

(184) These drugs should not be used together because of high rates of virologic failure:

Tenofovir, Abacavir

(184) Therapeutic Uses of Tenofovir

First-line NRTIs for treatment of HIV-1; Pregnant patients, all trimesters; Chronic HBV treatment and prophylaxis in immunocompromised patients

(184) _____ may cause hyperpigmentation, usually on the hands and/or soles of the feet.

Emtricitabine

(184) Therapeutic Uses of Integrase Strand Transfer Inhibitors (INSTIs)

Activity against HIV-1 and HIV-2

(184) _____ is administered once daily and requires a Cobicistat boost for effective treatment.

Elvitegravir

(184) Mechanism of Resistance to Integrase Strand Transfer Inhibitors (INSTIs)

Primary mutations in integrase gene (Q184R/H/K, or N155H); Additional secondary mutations

(184) _____ have a high barrier to resistance.

Dolutegravir, Bictegravir

(184) _____ have a lower barrier to resistance.

Raltegravir, Elvitegravir

(184) _____ can cause Injection site reactions.

Cabotegravir

(184) NRTI toxicities and mitochondrial toxicity

cardiomyopathy, peripheral neuropathy, pancreatitis, bone marrow suppression, and lactic acidosis

(184) _____ is formulated as a tablet for oral lead-in or bridging therapy.

Cabotegravir

(184) Mechanism of Action of Integrase Strand Transfer Inhibitors (INSTIs)

inhibit the insertion of proviral DNA into the host cell genome

(185) Examples of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Doravirine, Rilpivirine, Efavirenz, Nevirapine, Etravirine

(185) Mechanism of Action of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

bind to allosteric site on reverse transcriptase, inhibiting its polymerase activity; induce conformational change, decrease activity of the enzyme

(185) Mechanism of Resistance of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

occurs rapidly with monotherapy; Single amino acid changes in binding pocket confers high-level drug resistance. High-level cross-resistance occurs within the class

(185) Adverse Effects of Doravirine

Generally well tolerated

(185) Adverse Effects of Efavirenz

Neuropsych side effects, rash, Dizziness, abnormal dreams, headache, depression, insomnia

(185) Adverse Effects of Rilpivirine

Generally well tolerated; Depression, Headache, QTc prolongation. Avoid with PPIs

(185) Adverse Effects of Nevirapine

Hepatotoxicity, hepatic necrosis, rash

(185) _____ has a low barrier to resistance and is not recommended for initial ART

Nevirapine

(185) _____ has a higher barrier to resistance and is an ART option for treatment-experienced patients.

Etravirine

(185) Examples of HIV Protease Inhibitors

Atazanavir, Darunavir

(185) Adverse Effects of HIV Protease Inhibitors

nausea/vomiting/diarrhea, hyperglycemia/diabetes, Cushingoid fat redistribution

(185) Adverse Effects of Atazanavir

Jaundice, Cholelithiasis, Nephrolithiasis

(185) Adverse Effects of Darunavir

Skin rash, Caution in patients with h/o sulfonamide allergy, liver toxicity

(185) Bosted _____ twice daily is preferred for initial therapy in all trimesters of pregnancy.

HIV Protease Inhibitors

(185) _____ are substrates and inducers/inhibitors of CYPs. There is a high potential for drug interactions.

NNRTIs

(185) Mechanism of Action of HIV Protease Inhibitors

Reversible inhibitors of HIV-1 protease; Prevent proteolytic cleavage of HIV gag and pol proteins into a number of essential enzymes

(185) Examples of Entry Inhibitors

Maraviroc, Enfuvirtide, Fostemsavir, Ibalizumab

(185) _____ is a CCR5 Inhibitor with activity against CCR5-tropic strains of HIV-1 only.

Maraviroc

(185) Mechanism of Action of Maraviroc

Blocks binding of the HIV outer envelope protein gp120 to the CCR5 chemokine receptor

(185) Mechanism of Resistance to Maraviroc

Shift in tropism to CXCR4 or dual tropism; Mutations in the V3 loop of gp120 that allow virus binding in the presence of inhibitor

(185) Mechanism of Action of Enfuvirtide

36-amino acid synthetic peptide, binds HIV envelope protein gp41; Inhibits the conformational change in gp41 required for membrane fusion, preventing the fusion of HIV-1 virus with CD4 cells

(185) Mechanism of Resistance to Enfuvirtide

Mutations in the codon of the enfuvirtide binding domain of gp41

(185) Adverse Effects of Enfuvirtide

Frequent local cutaneous reactions (injection site) pain, erythema, induration, and nodules and twice daily dosing make long-term use difficult

(185) Mechanism of Action of Fostemsavir

Binds HIV-1 gp120 envelope adjacent to the gp120-CD4 binding site; prevents the gp120 conformational change which prevents attachment of CD4

(185) _____ is used for treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current ART due to resistance, intolerance, or safety considerations.

Fostemsavir, Lenacapavir

(185) Adverse Effects of Fostemsavir

Nausea (most common); Elevations of hepatic enzymes, especially in patients with HBV

(185) Mechanism of Action of Ibalizumab

Monoclonal antibody blocks domain 2; post-attachment inhibitor by binding CD4, which interferes with the post-attachment steps required for HIV entry into host cells

(185) _____ preserves normal immune function and is for heavily treatment-experienced adults.

Ibalizumab

(185) Adverse Effects of Lenacapavir

Generally well tolerated. Injection site reactions frequently reported

(185) Pre-Exposure Prophylaxis (PrEP)

For prevention of HIV-1 infection in adults who are at very high risk for acquiring HIV, such as individuals who engage in sexual activity within a high prevalence area or social network or intravenous drug users

(185) _____ is Pre-Exposure Prophylaxis (PrEP) given orally daily for men or women (long experience with this drug).

TDF-Emtricitabine

(185) _____ is Pre-Exposure Prophylaxis (PrEP) given orally daily for adolescents, transgender women, and men with bone and renal problems who are not eligible for TDF.

TAF-Emtricitabine

(185) _____ is Pre-Exposure Prophylaxis (PrEP) given I.M. in gluteal muscle every 2 months for adults (no renal or lipid monitoring is required).

Cabotegravir

(185) _____ is the preferred Pre-Exposure Prophylaxis (PrEP) for healthcare workers.

TDF-emtricitabine with dolutegravir or raltegravir

(185) Adverse Effects of Gender-affirming hormone therapies

hyperlipidemia, elevated cardiovascular risk, osteopenia

(185) All HIV-infected pregnant people should receive a combination _____ drug regimen, regardless of CD4 count or HIV RNA copy number

antepartum antiretroviral (ARV)

(185) _____ is given I.V. during labor (in pregnant patients) if patient has HIV RNA >1,000 copies/mL (or unknown HIV RNA) near delivery,

Zidovudine

(185) HIV Medication Combinations that should NOT be used

Zidovudine + Stavudine, Didanosine + Stavudine, Didanosine + Zalcitabine, Didanosine + Tenofovir, Lamivudine + Zalcitadine, Lamivudine + Emtricitabine, Triple NRTI therapy

(185) Mechanism of Resistance to HIV Protease Inhibitors

stepwise accumulation of mutations of the protease gene, leading to high-level resistance

(186) Systemic Lupus Erythematosus (SLE)

multisystem autoimmune disorder involving connective tissue & blood vessels

(186) Signs/Symptoms of Systemic Lupus Erythematosus (SLE)

Malar/Butterfly Rash - erythematous plaques, spares nasolabial folds; Discoid Rash - erythematous papules with adherent keratotic scaling; Arthritis - pain in 2 or more joints

(186) Signs/Symptoms of Dermatomyositis

Heliotrope rash & Grotton’s papules

(186) (189) Signs/Symptoms of Kawasaki Disease

Conjunctivitis, Rash, Adenopathy, Strawberry tongue, Hand and feet edema, Fever >5 days

(186) Signs/Symptoms of Behcet’s Disease

recurrent oral & genital lesions, uveitis